Enhancement of Bovine Leukemia Virus-Induced Syncytia Formation by Di- and Tripeptides

Voneche, V.; Callebaut, Isabelle; Lambrecht, Bénédicte; Brasseur, Robert; Burny, Arsène; Portetelle, Daniel

doi:10.1006/viro.1993.1034

Cited by 5 publications

(4 citation statements)

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“…The same mutational strategy has been used successfully to suppress the ability of tilted peptides to induce liposome fusion in vitro (19) and, when applied to the tilted peptides of the SIV and bovine leukemia virus (BLV) envelope glycoproteins, to reduce strongly or even abolish virus fusion processes (22,23). Here, likewise we show that an MBP-fused variant of 16K hPRL, characterized by mutations that respect the amino acid composition but disrupt the hydrophobicity gradient in the tilted peptide region, is less antiangiogenic than MBP-fused wild-type 16K hPRL.…”

Section: Discussionmentioning

confidence: 99%

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Prolactin/growth hormone–derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis

Nguyen

Tabruyn

Lins

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin͞growth hormone (PRL͞GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's ␤-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis. 16-kDa N-terminal fragment of prolactinA ngiogenesis, the formation of new blood vessels from preexisting ones, is crucial in both health and disease. Its involvement in tumor growth and metastasis (1) makes it an important potential target for anticancer therapy. Many angiogenesis inhibitors are cryptic fragments of endogenous molecules displaying no angiogenesis-related activity [angiostatin, endostatin, platelet factor-4 (PF-4), tumstatin, and thrombospondin (2)]. From some of these inhibitors, shorter peptides retaining antiangiogenic activity have been isolated, such as the PF-4 peptide 47-70 (3), endostatin fragments 2 and 5 (amino acids 60-70 and amino acids 171-183) (4), and tumstatin peptides T3 and T7 (amino acids 69-88 and amino acids 74-98) (5). This observation suggests that the antiangiogenic regions of these peptides may be exposed in the isolated fragments but buried in the full-length proteins.The 16-kDa N-terminal fragment of prolactin (16K PRL) is antiangiogenic in vitro (6-11) and in vivo. Generation of the 16K fragment from PRL has been attributed to cathepsin D (12). Its ability to prevent angiogenesis in tumor and retinopathy mouse models has raised interest in its potential therapeutic use (13-15). We have sought to identify in human 16K PRL (16K hPRL) a peptide that might be responsible for its antiangiogenic activity. Although the 16K fragments of the other three human PRL͞GH-family members are also potently antiangiogenic (16), the sequence similarity of these fragments is low (Ϸ35% similarity between all mammalian PRL͞GH sequences). This consideration led us to seek a peculiar common structural feature rather than a similar sequence.Tilted (or oblique-oriented) peptides are short helical peptides (11 to 20 aa long) characterized by a peculiar distribution of hydrophobic residues: they are amphipathic ...

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Section: Discussionmentioning

confidence: 99%

“…Its predicted oblique insertion across the lipid-water interface is proposed to trigger local phospholipid disorganization and to generate a new lipid phase favoring fusion (17). Modification of the insertion angle of the bovine leukemia virus (BLV) and SIV peptides is apparently sufficient to abolish fusion (22,23).…”

Section: Discussionmentioning

confidence: 99%

Prolactin/growth hormone–derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis

Nguyen

Tabruyn

Lins

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…The substitution of the T for E residues at position 14 in any of the two peptides (p5→p3 or p6→p4) or the scrambling of the amino acid sequence of p5 (randomizing p5 sequence) abolished the effect of enhancement, thus showing the specificity of the interaction and its amino acid sequence dependence. Enhancement of virus infectivity was described before for 2- to 3-mer peptides in bovine leukaemia virus (Voneche et al ., 1993 ) and for 4-mer peptides in xenotropic murine retrovirus (Suk & Long, 1983 ) but not for larger peptides. To our knowledge, only a peptide sequence with antiviral activity against grass carp haemorrhage reovirus has been selected before from a nona-peptide library displayed on phages (Wang et al ., 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Salmonid viral haemorrhagic septicaemia virus: fusion-related enhancement of virus infectivity by peptides derived from viral glycoprotein G or a combinatorial library

Más¹,

Pérez²,

Encinar³

et al. 2002

Journal of General Virology

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To search for enhancers and/or inhibitors of viral haemorrhagic septicaemia virus (VHSV, a salmonid rhabdovirus) infectivity, a total of 51 peptides from a pepscan of viral envelope protein G, a recombinant peptide from protein G (frg11) and 80 peptide mixtures from an α-helix-favoured combinatorial library were screened. However, contrary to what occurs in many other enveloped viruses, only peptides enhancing rather than inhibiting VHSV infectivity were found. Because some of the enhancer pepscan G peptides and frg11 were derived from phospholipid-binding or fusionrelated regions identified previously, it was suggested that enhancement of virus infectivity might be related to virus-cell fusion. Furthermore, enhancement was significant only when the viral peptides were pre-incubated with VHSV at the optimal low pH of fusion, before being adjusted to physiological pH and assayed for infectivity. Enhancement of VHSV infectivity caused by the preincubation of VHSV with peptide p5 (SAAEASAKATAEATAKG), one of the individual enhancer peptides defined from the screening of the combinatorial library, was independent of the preincubation pH. However, it was also related to fusion because the binding of p5 to protein G induced VHSV to bypass the endosome pathway of infection and reduced the low-pH threshold of fusion, thus suggesting an alternative virus entry pathway for p5-VHSV complexes. Further investigations into VHSV enhancer peptides might shed some light on the mechanisms of VHSV fusion.

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“…Recently, synthetic peptides with amino acid sequences corresponding to the N terminus of the transmembrane glycoprotein gp41 of HIV type 1 (HIV-1) were also found to inhibit HIV glycoprotein-induced membrane fusion (45,55). In contrast to the inhibitory effect of such N-terminal peptides, similar di-and tripeptides surprisingly exert an enhancer effect in bovine leukemia virus glycoprotein-mediated syncytium formation (59).…”

Section: Discussionmentioning

confidence: 99%

Requirement of N-terminal amino acid residues of gp41 for human immunodeficiency virus type 1-mediated cell fusion

Schaal

Klein

Gehrmann

et al. 1995

J Virol

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An expression vector was designed to test the structural requirements of the gp41 N terminus for human immunodeficiency virus type 1-induced membrane fusion. Mutations in the region coding for the N terminus of gp41 were found to disrupt glycoprotein expression because of deleterious effects on the Rev-responsive element (RRE). Insertion of an additional RRE in the 3-noncoding sequence of env made possible efficient glycoprotein expression, irrespective of the mutations introduced into the RRE in the natural location. This permitted the insertion of the unique restriction site SpeI within the N-terminal sequences of gp41, allowing convenient and efficient mutation of the gp41 N terminus by using double-stranded synthetic oligonucleotides. Mutants with deletions of 1 to 7 amino acids of the N terminus were constructed. Expression and cleavage of all mutants were confirmed by Western immunoblot analysis with anti-gp41 antibodies. The capability of mutants to induce membrane fusion was monitored following transfection of HeLa-T4 ؉ cell lines with wild-type and mutant expression vectors by electroporation and microinjection. The efficiency of cell-fusing activity decreased drastically with deletion of 3 and 4 amino acids and was completely lost with deletion of 5 amino acids. Cotransfection of the parent and mutant expression vectors resulted in reduced cell-fusing activity. The extent of this dominant interference by mutant glycoprotein paralleled the decrease in cell-fusing activity of the mutants alone. This suggests the existence of a specific N-terminal structure required for fusing activity. However, there does not appear to be a stringent requirement for the precise length of the N terminus. This finding is supported by the length variation of this region among natural human immunodeficiency virus type 1 isolates and is in contrast to the apparent stringency in the length of analogous N-terminal structures of influenza A virus and paramyxovirus fusion glycoproteins.

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Enhancement of Bovine Leukemia Virus-Induced Syncytia Formation by Di- and Tripeptides

Cited by 5 publications

References 0 publications

Prolactin/growth hormone–derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis

Prolactin/growth hormone–derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis

Salmonid viral haemorrhagic septicaemia virus: fusion-related enhancement of virus infectivity by peptides derived from viral glycoprotein G or a combinatorial library

Requirement of N-terminal amino acid residues of gp41 for human immunodeficiency virus type 1-mediated cell fusion

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